The biochemical and physiological effects of in situ isolated lung perfusion was investigated in dogs using the anticancer agent, doxorubicin. During perfusion and for the first 2 weeks post perfusion, biological samples were collected for various enzymatic analyses in order to elucidate possible correlations between administered drug dosage and subsequent toxicity. Two weeks post perfusion, a right-lung pneumonectomy was performed on surviving dogs in order to assess the functional capacity of the perfused left lungs. A dose-related morbidity was seen in the animals following lung perfusion. Lactate dehydrogenase activity in the perfusate increased as dose was increased indicating tissue damage during the perfusion. Up to 7 days post-perfusion, marked changes were seen in the serum protein concentrations although these were independent of doxorubicin concentrations. Serum lactate dehydrogenase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase, showed a dose-dependent increase 2 hrs and 1 day after the lung perfusion. Plasma angiotensin converting enzyme activities up to 14 days post-perfusion depended upon the concentrations of doxorubicin used during the perfusion. The study has demonstrated that doxorubicin produces dose-dependent damage to the pulmonary tissue. However, the observed injury only appeared life-threatening at perfusate drug concentrations in excess of 20 nmol/ml. In situ lung perfusion for the treatment of unresectable pulmonary tumors may be clinically applicable.